Summary:Our laboratory utilizes multiple techniques to determine the effects of age, gender and lifestyle habits on cardiovascular (CV) performance at rest and during exercise. (A) Longitudinal changes of maximal aerobic capacity (VO2max) were determined in nearly 1,400 Baltimore Longitudinal Study of Aging (BLSA) volunteers without evident cardiac disease, using mixed effects statistical analysis. Per decade, longitudinal declines in VO2max were generally greater than cross-sectional declines, especially in older decades. Gender differences in both absolute VO2max and rates of decline (men>women) are markedly attenuated when VO2max was normalized for fat-free mass rather than body weight (Circulation. 2005;112(5):674-82). (B) The longitudinal decline in VO2max was determined in 42 older male endurance athletes, initially 64 (plus or minus) 6 years old. Over a mean follow-up of 7.8 years, VO2max declined by 22%, triple the decrease predicted by the baseline cross-sectional data. Within the overall sample, training status during follow-up had a major effect on the change in VO2max: the 6 men who continued to train vigorously had no significant decline in VO2max (0.28%/yr.), the 20 that trained at a lower intensity declined by 2.6% / yr, and the 14 who stopped training declined 4.6% / yr. Thus, physical activity patterns have a major impact on the long-term changes in maximal aerobic capacity in older athletes. (C) Left ventricular thickness, mass and chamber dimensions were measured in 336 healthy, normotensive adults (mean age 56+/-18 years, 200 women, 136 men) by magnetic resonance imaging (MRI). We found that the left ventricle becomes more spherical with age in normal adults because of reduced length. In women, this is associated with an increased wall thickness which offsets the decrease in length, resulting in left ventricular mass not changing with age. In men, wall thickness does not compensate for the increased sphericity, resulting in decreased left ventricular mass with age (Am J Cardiol 2002;90:1231-1236). (D) Ejection fraction (EF) acutely increases during exercise, but the EF reserve decreases with advancing age. EF is inversely related to the index of the interaction between arterial and ventricular properties, defined by the ratio of arterial elastance (EaI) to left ventricular systolic elastance (ELVI). We noninvasively characterized the arterial-ventricular coupling index EaI/ELVI and its two determinants at rest and during graded exercise in 136 healthy men and 103 healthy women (age range 21-87 years) from the Baltimore Longitudinal Study of Aging. We found that age-associated differences in EaI/ELVI occur in both genders during exercise, with less optimal coupling in older compared to younger subjects, which may help to explain the age deficit in maximal exercise EF. We also found that the mechanisms underlying the sub-optimal coupling in older adults differed between men and women (J Am Coll Cardiol. 2004;44(3):611-617). (E)Diastolic heart failure is common in older women, often occurs following longstanding hypertension, and is characterized by reduced cardiovascular reserve during exercise. Recent insights suggest that arterial-ventricular coupling (AV-C), which is an important determinant of cardiovascular performance, may play an important role in the pathophysiology of diastolic heart failure. AV-C was measured at rest and with graded cycle ergometry in 142 normotensive and 35 hypertensive women free from overt cardiovascular disease. AV-C was 26% lower in hypertensive than normotensive women at rest. The AV-C reserve, calculated as the difference in AV-C between rest and peak exercise was also smaller in the hypertensive than normotensive women (0.2plus or minus 0.03 vs 0.28 plus or minus 0.01, p< 0.001). Thus, examination of AV-C at rest and with exercise provides mechanistic insights into why hypertension may predispose older women to diastolic heart failure. (F) Although it is well established that evidence of coronary ischemia during treadmill exercise is associated with an increased likelihood of future coronary events (angina pectoris, myocardial infarction or death), even in clinically healthy populations, less is known about the prognostic significance of the absence of objective evidence of ischemia, as determined from electrocardiography (ECG), tomographic thallium scintigraphy, or both. We performed maximal treadmill exercise ECG and thallium scintigraphy (201Tl) in 697 asymptomatic volunteers (57% men) with no clinical history of coronary heart disease from the Baltimore Longitudinal Study of Aging. The average age was 62 plus or minus 12 years. 289 subjects had evidence of ischemia on the stress test: 193 had a positive ECG, and 175 a positive Tl201. Over a mean follow-up period of 6.7 years, cardiac events developed in 11% of subjects. Events occurred in 10% of individuals with a negative ECG, 8% of those with a negative 201Tl, and 7% of those with concordant negative 201Tl and ECG. After adjusting for age and other covariates, negative ECG was not associated (p=NS), whereas a negative 201Tl was weakly associated (hazard ratio=0.62, 95%CI 0.37-1.04, p=0.07) with the absence of future events. Concordant negative ECG and 201Tl was an independent predictor of freedom from events (hazard ratio=0.58, 95% CI 0.34-0.97, p=0.03), with a sensitivity, specificity and negative predictive value of 62%, 61% and 93% respectively. Thus, in healthy individuals, the concordant absence of ischemia on both ECG and 201Tl provides independent prognostic information. (G) Heart failure with normal ejection fraction (HFnEF) often develops in patients with hypertensive-left ventricular hypertrophy (H/LVH) and involves multiple abnormalities. It remains unclear which features best distinguish patients from these 2 groups. We performed a case-control cross-sectional study comparing HFnEF patients (n=37), H/LVH subjects without HF (n=40), and normotensive controls without LVH (CON, n=56). Comprehensive echo-Doppler and pressure analysis was performed. All HFnEF subjects had hypertension and LVH. They displayed vascular and systolic-ventricular stiffening, and abnormal diastolic function compared with CON; however, most abnormalities were similarly altered in H/LVH subjects, and poorly distinguished between the HFnEF and H/LVH groups. HFnEF had greater concentric LVH, higher estimated mean pulmonary-wedge pressure (20 vs 16 mmHg), and shorter relaxation than H/LVH. HFnEF, but not H/LVH, exhibited left atrial (LA) dilation/dysfunction. The best separation between HFnEF and H/LVH was provided by a numerical product of LV mass index and maximal LA volume (84% sensitivity and 82% specificity). Thus, accentuated LVH and LA dilation/failure better identify HFnEF from H/LVH patients than do indexes of diastolic, systolic, or vascular function. This may help in defining this population for clinical trials and in assessing clinical prognosis in HFnEF (J Am Coll Cardiol. 2007;49:198-207).